Innate Immunity in Newborns

Chapter 6 This chapter outlines the concepts of innate immunity, inflammation, and wound healing. Innate immunity refers to the body's initial defense mechanisms against invasion and injury. Inflammation is the body's response to injury and infection, aimed at protecting and healing the body. Wound healing involves several phases, including hemostasis, inflammation, tissue formation, and remodeling. Bullet points Innate Immunity in Newborns  Newborns have limited innate immune function  Inflammatory responses are transiently depressed  Neutrophils lack chemotaxis and fluidity in the plasma membrane  Complement levels, especially alternative pathway components, are diminished  Monocyte chemotaxis is delayed  Newborns are predisposed to infections and have compromised responses  Breast milk facilitates the establishment of the gut microbiome Innate Immunity in the Elderly  Elderly have normal numbers of cells but diminished cellular function  Increased risk for chronic inflammation and decreased phagocytic function  Predisposing causes include chronic illness and medication use  Decreased subcutaneous fat and atrophied epidermis increase risks  The aging immune system diminishes vaccine effectiveness Human Defense Mechanisms  Innate defenses include skin and mucous membranes  Inflammation is a secondary defense response Innate Immunity  Neonates may have temporarily reduced inflammatory function  Elderly persons may experience impaired wound healing  There are three layers of human defense: physiologic barriers, the inflammatory response, and adaptive immunity  Physical barriers, like the skin and mucous membranes, are the first line of defense  Antibacterial peptides provide a biochemical barrier against pathogens  Commensal microorganisms in the body provide protection and aid in digestion  The inflammatory response is a rapid and nonspecific protective response in vascular tissues  Inflammation is characterized by redness, swelling, heat, pain, and loss of function  Inflammation is mediated by complement system, clotting system, and kinin system  The complement system can be activated by antigen-antibody reactions or bacterial polysaccharides  The clotting system stops bleeding and provides a mesh for repair  The kinin system produces bradykinin, causing vascular permeability, smooth muscle contraction, and pain  Control of inflammation involves enzymes and localizes the response  Many different cells are involved in the inflammatory process, including mast cells, endothelial cells, phagocytes, lymphocytes, and natural killer cells  Cells express pattern recognition receptors that recognize molecules from microorganisms  Toll-like receptors and nucleotide-binding-like receptors are examples of pattern recognition receptors Mechanisms of the innate immune system  Innate immune cells secrete cytokines, which activate other cells and regulate inflammation  Cytokines include chemokines, interleukins, interferons, and other molecules  Chemokines attract leukocytes and other cells to promote phagocytosis and wound healing  Interleukins promote or inhibit inflammation and stimulate the growth and differentiation of leukocytes  Interferons stimulate healthy cells to produce substances that prevent viral infection Mediators of the inflammatory response  Mast cells and basophils release histamine, chemotactic factors, prostaglandins, leukotrienes, and plateletactivating factor  Histamine increases vascular permeability and dilation of capillaries  Endothelial cells regulate blood flow and promote leukocyte exit from vessels  Platelets release mediators that facilitate and control inflammation Phagocytic cells and their functions  Polymorphonuclear neutrophils (PMNs) are the predominant phagocytic cells in early inflammation and they migrate to inflammatory sites  Eosinophils control inflammation and destroy parasitic organisms  Macrophages are highly phagocytic and promote wound healing  Dendritic cells process antigens, transport them to lymph nodes and spleen, and present them to T cells to form antibodies Phagocytosis process and opsonization  Phagocytosis involves recognition, engulfment, formation of phagosomes and phagolysosomes, and destruction of pathogens  Opsonins enhance phagocytosis by coating antigens, marking them for phagocytosis Acute Inflammation  Acute inflammation usually resolves within 8 to 10 days  Local manifestations include redness, heat, swelling, pain, and loss of function  Systemic effects include fever, leukocytosis, and an increase in plasma proteins Chronic Inflammation  Chronic inflammation can be a continuation of acute inflammation or occur as a distinct process  Characterized by dense infiltration of lymphocytes and macrophages  Granuloma formation protects the body from further tissue damage Wound Healing  Resolution refers to the return of tissue to normal structure and function  Repair involves the formation of scar tissue  Resolution occurs when little tissue has been lost, repair occurs when extensive damage has occurred  Healing involves reconstructive and maturation phases  Dysfunctional wound healing can be caused by various factors  Dehiscence is when the wound pulls apart at the suture line  Contracture is a structural deformity caused by excessive shortening of collagen Key Terms  Examples include abscess, acute inflammation, antibody, antigen, fever, cytokine, granuloma, wound healing, dehiscence, contracture Immune Response and Inflammation  Inflammation is a response to injury or infection  It involves vascular changes like increased vascular permeability and vasodilation  Vascular changes lead to redness (rubor) and edema  Inflammation is mediated by various molecules, including histamine, interleukins, and tumor necrosis factor-alpha (TNF-a)  Inflammation leads to recruitment of white blood cells, such as neutrophils, monocytes, and lymphocytes  Phagocytes, such as macrophages and neutrophils, play a major role in phagocytosis and clearance of pathogens  Complement system and opsonins enhance the recognition and destruction of pathogens  Resolution of inflammation involves a complex interplay of multiple factors